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A pro-angiogenic degradable Mg-poly(lactic-co-glycolic acid) implant combined with rhbFGF in a rat limb ischemia model.

作者信息

Bao Hanmei, Lv Feng, Liu Tianjun

机构信息

Institute of Biomedical Engineering, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin Key Laboratory of Biomedical Materials, Tianjin 300192, China; Department of Clinical Pharmacology, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China.

Institute of Biomedical Engineering, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin Key Laboratory of Biomedical Materials, Tianjin 300192, China.

出版信息

Acta Biomater. 2017 Dec;64:279-289. doi: 10.1016/j.actbio.2017.09.033. Epub 2017 Sep 23.


DOI:10.1016/j.actbio.2017.09.033
PMID:28951330
Abstract

UNLABELLED: Site-specific controlled release of exogenous angiogenic growth factors, such as recombinant human basic fibroblast growth factor (rhbFGF), has become a promising approach to improve peripheral vascular disease. Here, we have developed an implant composed of spiral magnesium (Mg) and a coating made using poly(lactic-co-glycolic acid) (PLGA) with encapsulated rhbFGF (Mg-PLGA-rhbFGF). The encapsulated protein could release continually for 4weeks with well preserved bioactivity. We compared the angiogenic effect produced by Mg-PLGA-rhbFGF with that of a PLGA implant loaded with rhbFGF (PLGA-rhbFGF). The incorporation of Mg in the implant raised the microclimate pH in the polymer, which preserved the stability of rhbFGF. Mg-PLGA-rhbFGF exhibited advantages over PLGA-rhbFGF implant in terms of a cytocompatibility evaluation. An in vivo angiogenesis test further confirmed the efficacy of released rhbFGF. HE, CD31 and α-SMA staining revealed that the controlled release of rhbFGF from the Mg-PLGA-rhbFGF implant was superior in promoting angiogenesis compared with that of the PLGA-rhbFGF implant. Four weeks post-implantation, the capillary density of the Mg-PLGA-rhbFGF group was significantly higher than that of the PLGA-rhbFGF, control and the normal group (p<0.05, p<0.01 and p<0.01, respectively). Furthermore, the limb blood perfusion ratios of the Mg-PLGA-rhbFGF and PLGA-rhbFGF groups were dramatically increased, at 99.1±2.9% and 80.7±3.2%, respectively, whereas the ischemic limb did not recover in the control group. The biocompatibility of the implants was also evaluated. In conclusion, Mg-PLGA-based, sustained local delivery of rhbFGF promotes post-ischemic angiogenesis and blood flow recovery. The results suggest potential therapeutic usefulness of Mg-PLGA-rhbFGF for tissue ischemia. STATEMENT OF SIGNIFICANCE: Magnesium (Mg)-based implant has been already used in patients with critical limb ischemia. Site-specific controlled release of recombinant human basic fibroblast growth factor (rhbFGF), has become a promising approach to improve peripheral vascular disease. We report here on a novel combination implant composed of spiral magnesium and a coating made using poly(lactic-co-glycolic acid) (PLGA) with encapsulated rhbFGF (Mg-PLGA-rhbFGF). The preparation method does not involve any complex processes and results in a high encapsulation efficiency (approximately 100%). The degradation of metal Mg raise the microclimate pH in the PLGA polymer, which could well preserve the bioactivity of rhbFGF incorporated in the implant. Mg-PLGA-based, sustained local delivery of rhbFGF promotes post-ischemic angiogenesis and blood flow recovery in rat limb ischemic model. This work marks the first report for controlled release of rhbFGF in combination with metal Mg, and suggests potential therapeutic usefulness of Mg-PLGA-rhbFGF for tissue ischemia.

摘要

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A pro-angiogenic degradable Mg-poly(lactic-co-glycolic acid) implant combined with rhbFGF in a rat limb ischemia model.

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引用本文的文献

[1]
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Mater Today Bio. 2021-12-20

[2]
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[3]
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[4]
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